untitled SHORT REPORT Detection of antibodies to citrullinated tenascin C in patients with early synovitis is associated with the development of rheumatoid arthritis Karim Raza,1,2 Anja Schwenzer,3 Ma[.]
Early arthritis SHORT REPORT Detection of antibodies to citrullinated tenascin-C in patients with early synovitis is associated with the development of rheumatoid arthritis Karim Raza,1,2 Anja Schwenzer,3 Maria Juarez,1 Patrick Venables,3 Andrew Filer,1 Chris D Buckley,1,2 Kim S Midwood3 To cite: Raza K, Schwenzer A, Juarez M, et al Detection of antibodies to citrullinated tenascin-C in patients with early synovitis is associated with the development of rheumatoid arthritis RMD Open 2016;2: e000318 doi:10.1136/ rmdopen-2016-000318 ▸ Prepublication history and additional material is available To view please visit the journal (http://dx.doi.org/ 10.1136/rmdopen-2016000318) KR and AS contributed equally to this work Received 17 June 2016 Revised 12 September 2016 Accepted 20 September 2016 For numbered affiliations see end of article Correspondence to Dr Kim S Midwood; kim.midwood@kennedy.ox ac.uk Early treatment of rheumatoid arthritis (RA) results in more effective disease suppression and can be key to a successful patient response However, not all people who exhibit early synovitis develop RA; for example, in some, synovial inflammation resolves spontaneously.1 The factors that drive RA development remain unclear and clinical tools to predict RA development are imperfect Tenascin-C is a proinflammatory matrix molecule that is absent from healthy joints but highly expressed in the joints of patients with RA.2 We identified an immunodominant peptide in citrullinated tenascin-C, cTNC5, antibodies against which are detected in around half of the patients with RA, and can be found years before disease onset in some individuals.4 Here, we sought to determine if anti-cTNC5 antibodies can discriminate among people with early synovial inflammation those who develop RA and those with other outcomes Sera from 263 patients in the Birmingham early arthritis cohort were analysed Patients were disease-modifying antirheumatic drug (DMARD) naïve with clinically apparent synovitis of ≥1 joint and with inflammatory joint symptoms of ≤3 months’ duration Patients were followed for 18 months to ensure development of full disease phenotype and to allow any resolving arthritis time to resolve At 18 months, patients were assigned to the following outcome categories: persistent RA according to the American College of Rheumatology (ACR) 2010 criteria5 (RA, n=101), persistent non-RA arthritis (PNRA, n=66) and resolving arthritis (no clinically apparent joint swelling, no DMARD/steroid use in the previous months, n=96) Demographic and clinical parameters were recorded, and patients with RA divided into anti-cyclic citrullinated peptide (anti-CCP) antibody positive and negative subsets.6 Antibodies recognising cTNC5 or the noncitrullinated control peptide (rTNC5) were analysed by ELISA as described.4 Anti-cTNC5 antibodies were found in 40.6% of people with early synovitis who went on to develop RA, but were detected in a low proportion of people who developed PNRA (6.1%), or whose disease resolved (3.1%) No significant antibody response to rTNC5 was detected ( p=0.527) (table 1, see online supplementary figure S1) Anti-cTNC5 antibodies were significantly more prevalent in anti-CCP antibody positive compared with anti-CCP antibody negative patients with RA (81.3% vs 3.8%, p